Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3MR73R)

• DOT Name: Radial spoke head 1 homolog (RSPH1)
• Synonyms: Cancer/testis antigen 79; CT79; Male meiotic metaphase chromosome-associated acidic protein; Meichroacidin; Testis-specific gene A2 protein
• Gene Name: RSPH1
• Related Disease:
  Idiopathic bronchiectasis
  Primary ciliary dyskinesia 24
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia
  Congenital alveolar dysplasia
  Sickle-cell anaemia
• UniProt ID: RSPH1_HUMAN
• PDB ID: 8J07
• Pfam ID: PF02493
• Sequence:
  MSDLGSEELEEEGENDIGEYEGGRNEAGERHGRGRARLPNGDTYEGSYEFGKRHGQGIYK
  FKNGARYIGEYVRNKKHGQGTFIYPDGSRYEGEWANDLRHGHGVYYYINNDTYTGEWFAH
  QRHGQGTYLYAETGSKYVGTWVNGQQEGTAELIHLNHRYQGKFLNKNPVGPGKYVFDVGC
  EQHGEYRLTDMERGEEEEEEELVTVVPKWKATQITELALWTPTLPKKPTSTDGPGQDAPG
  AESAGEPGEEAQALLEGFEGEMDMRPGDEDADVLREESREYDQEEFRYDMDEGNINSEEE
  ETRQSDLQD
• Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
• Tissue Specificity: Expressed in trachea, lungs, airway brushings, and testes.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Idiopathic bronchiectasis	DISZ7YNI	Definitive	Genetic Variation	[1]
Primary ciliary dyskinesia 24	DISHBMBD	Definitive	Autosomal recessive	[2]
Primary ciliary dyskinesia 1	DISPGX6H	moderate	CausalMutation	[1]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[3]
Congenital alveolar dysplasia	DIS1IYUN	Disputed	Genetic Variation	[4]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[5]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Radial spoke head 1 homolog (RSPH1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Radial spoke head 1 homolog (RSPH1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Radial spoke head 1 homolog (RSPH1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Radial spoke head 1 homolog (RSPH1).	[9]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Radial spoke head 1 homolog (RSPH1).	[10]

References

• [1] Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype.Am J Respir Crit Care Med. 2014 Mar 15;189(6):707-17. doi: 10.1164/rccm.201311-2047OC.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects. Am J Hum Genet. 2013 Sep 5;93(3):561-70. doi: 10.1016/j.ajhg.2013.07.013. Epub 2013 Aug 29.
• [4] Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a Primary Ciliary Dyskinesia Phenotype.Am J Respir Cell Mol Biol. 2019 Sep;61(3):312-321. doi: 10.1165/rcmb.2017-0387OC.
• [5] Sensitivities to Thermal and Mechanical Stimuli: Adults With Sickle Cell Disease Compared to Healthy, Pain-Free African American Controls.J Pain. 2020 Sep-Oct;21(9-10):957-967. doi: 10.1016/j.jpain.2019.11.002. Epub 2019 Nov 13.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.